A feasibility study for enrichment of highly aggressive cancer subpopulations by their biophysical properties via dielectrophoresis enhanced with synergistic fluid flow

Temple Anne Douglas, Jaka Cemazar, Nikita Balani, Daniel C. Sweeney, Eva M. Schmelz, Rafael V. Davalos

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

A common problem with cancer treatment is the development of treatment resistance and tumor recurrence that result from treatments that kill most tumor cells yet leave behind aggressive cells to repopulate. Presented here is a microfluidic device that can be used to isolate tumor subpopulations to optimize treatment selection. Dielectrophoresis (DEP) is a phenomenon where particles are polarized by an electric field and move along the electric field gradient. Different cell subpopulations have different DEP responses depending on their bioelectrical phenotype, which, we hypothesize, correlate with aggressiveness. We have designed a microfluidic device in which a region containing posts locally distorts the electric field created by an AC voltage and forces cells toward the posts through DEP. This force is balanced with a simultaneous drag force from fluid motion that pulls cells away from the posts. We have shown that by adjusting the drag force, cells with aggressive phenotypes are influenced more by the DEP force and trap on posts while others flow through the chip unaffected. Utilizing single-cell trapping via cell-sized posts coupled with a drag-DEP force balance, we show that separation of similar cell subpopulations may be achieved, a result that was previously impossible with DEP alone. Separated subpopulations maintain high viability downstream, and remain in a native state, without fluorescent labeling. These cells can then be cultured to help select a therapy that kills aggressive subpopulations equally or better than the bulk of the tumor, mitigating resistance and recurrence.

Original languageEnglish
Pages (from-to)1507-1514
Number of pages8
JournalElectrophoresis
Volume38
Issue number11
DOIs
StatePublished - Jun 2017
Externally publishedYes

Funding

This work was supported by NIH 5R21 CA173092-01, Isolation and enrichment of tumor stem cells using contactless dielectrophoresis and CIT MF13-037-LS, Use of Electric Fields for the Isolation of Tumor Initiating Cells and Other Rare Cells. We would also like to acknowledge Virginia Biosciences Health Research Corporation (VBHRC) and NSF IGERT DGE-0966125 MultiSTEPS.

Keywords

  • Biophysics
  • Cell separation
  • Heterogeneity
  • Microfluidics
  • Tumor

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